Dendrimers and supramolecular chemistry.

S ince their introduction in 1985 by Tomalia et al. (1) and Newkome et al. (2), dendrimers have attracted much attention because of their fascinating structure and unique properties (3, 4). Dendrimers are globular, size monodisperse macromolecules in which all bonds emerge radially from a central focal point or core with a regular branching pattern and with repeat units that each contribute a branch point. Not all regularly branched molecules are dendrimers because properties of the dendritic state (4), such as core encapsulation (5, 6) and unusually low intrinsic viscosity in solution (7), are reached only when globularity is achieved at a certain generation or size threshold. Therefore, many lowgeneration dendrons or the early cascade molecules of Vögtle and coworkers (8) are too small to exhibit the properties of dendrimers, but they are frequently used as branched oligomeric building blocks in their construction, and have a size relationship to dendrimers somewhat akin to that between oligomers and polymers. Two distinct synthetic methodologies have been used for the preparation of dendrimers: the divergent approach (1, 2), in which growths starts at the core and proceeds radially outward toward the dendrimer periphery, and the convergent approach, (9, 10) in which growth starts at what will become the periphery of the dendrimer proceeding inward. The two methodologies are complementary and neither is generally better, the choice of synthetic approach being usually justified by the features desired for the target molecule, the chemistry available for growth, and the specific building blocks used in the construction of the dendritic framework. In general, the convergent approach provides better overall structural control, in part as a result of its enhanced potential for purification at intermediate stages of growth, and, in part, as a result of its innate ability to introduce differentiated functionalities at the focal point and the periphery of the dendrimer. In contrast, purity and structural uniformity are harder to maintain in the divergent approach, because the number of reactions that must be completed at each step of growth increases exponentially requiring large excesses of reagents, but the process is better suited not only for syntheses on a larger scale but also for the preparation of high-generation dendrimers. Although the majority of the dendrimers prepared to-date have been built of covalent bonds (3, 10), many noncovalent dendrimers (3, 11) have also been prepared by a variety of selfassembly processes involving, for example, hydrogen bonding (12) or supramolecular coordination chemistry (13). Relating the concepts of dendrimers and supramolecular chemistry (14) in this article requires more that just a consideration of molecules resulting from supramolecular construction. The unique layered architecture of dendrimers, their globular shape, highly controlled size, radially controlled chemical make-up, multivalent periphery, variable inner volume, and controlled intramolecular dynamics endow dendrimers with unique features and provide them with the ability to morph into a variety of virtual supramolecular arrangements in response to external stimuli. Unlike collections of small molecules, which might require supramolecular assembly to deliver function, dendrimers can simply use internal dynamics to arrange their multiple and interconnected components in ways that minimize free energy (15) and afford specific functions. Such intramolecular reorganizations may lead to shape or volume changes, the creation of internal microenvironments, the cooperative organization of surface or inner functionalities, the concentration or exclusion of substrate from the molecular ‘‘cavity’’ of dendrimers, or the formation of defined multimolecular assemblies.